The unusual temperature-dependent excited-state dynamics of a stilbene-antibody complex reported by Simeonov et al. are explored using theoretical methods. The anomalous temperature-dependent fluorescence emission and lifetime are shown to be the result of interplay among temperature-modulated protein flexibility, the excited-state potential surface for the stilbene central twist, and changes in the stilbene charge distribution upon excitation. Stilbene is found to possess a similar geometry and orientation within the antibody binding pocket at all temperatures in the ground state and at low temperatures (approximately 240 K) in the excited state. At higher temperatures (approximately 260 K), the excited-state conformation twists around the central double bond and adopts an alternate orientation within the binding pocket. These changes result from protein side chain and loop motions that are frozen out at lower temperatures and account for the observed red shift of the fluorescence emission spectrum (a calculated shift of 3.8 kcal mol-1 compares favorably with the approximately 5 kcal.mol-1 observed experimentally). Approximately 3.0 kcal mol-1 of this stabilization is global in nature and is not attributable to specific local interactions. Local interactions between stilbene and Tyr-B39 contribute approximately 0.8 kcal mol-1 to the fluorescence shift. The primary structural change in simulations of the high temperature excited state involves a decrease in the stilbene-tyrosine distance and a relative change in orientation of the aromatic rings. We identify several nearby charged residues that contribute to the fluorescence emission shift and provide targets for mutagenesis to probe the temperature-dependent dynamics of protein-chromophore interactions.